Amirkhanzadeh Barandouzi Zahra, Bruner Deborah W, Miller Andrew H, Paul Sudeshna, Felger Jennifer C, Wommack Evanthia C, Higgins Kristin A, Shin Dong M, Saba Nabil F, Xiao Canhua
School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta, GA, 30322, USA.
School of Medicine, Emory University, 201 Dowman Dr, Atlanta, GA, 30322, USA.
Brain Behav Immun Health. 2023 Jun 4;30:100649. doi: 10.1016/j.bbih.2023.100649. eCollection 2023 Jul.
Head and neck cancer (HNC) patients may experience multiple co-occurring neuropsychological symptoms (NPS) cluster, including fatigue, depression, pain, sleep disturbance, and cognitive impairment. While inflammation has been attributed as a key mechanism for some of these symptoms, its association with the NPS as a cluster of symptoms is unknown. Thus, the aim of this study was to examine the association between peripheral inflammation and NPS cluster among HNC patients over cancer treatment (radiotherapy with or without chemotherapy).
HNC patients were recruited and followed at pre-treatment, end of treatment, three months and one-year post-treatment. Plasma inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNFA), soluble tumor necrosis factor receptor-2 (sTNFR2), interleukin-1 beta (IL1-β), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), and interleukin-1 receptor antagonist (IL-1RA) and patient-reported NPS cluster were collected at the 4 time points. Associations between inflammatory markers and the NPS cluster were analyzed using linear mixed-effects models and generalized estimating equations (GEE) models controlling covariates.
147 HNC patients were eligible for analysis. 56% of the patients received chemoradiotherapy as treatment. The highest NPS cluster score was reported at the end of treatment, which gradually decreased over time. An increase in inflammatory markers including CRP, sTNFR2, IL-6 and IL-1RA was associated with higher continuous NPS cluster scores (p<0.001, p = 0.003, p<0.001, p<0.001; respectively). GEE further confirmed that patients with at least two moderate symptoms had elevated sTNFR2, IL-6, and IL-1RA (p = 0.017, p = 0.038, p = 0.008; respectively). Notably, this positive association between NPS cluster and inflammatory markers was still significant at one-year post-treatment for CRP (p = 0.001), sTNFR2 (p = 0.006), and IL-1RA (p = 0.043).
Most HNC patients experienced NPS clusters over time, especially immediately after the end of treatment. Elevated inflammation, as represented by inflammatory markers, was strongly associated with worse NPS cluster over time; this trend was also notable at one-year post-treatment. Our findings suggest that peripheral inflammation plays a pivotal role in the NPS cluster over cancer treatment, including long-term follow-ups. Interventions on reducing peripheral inflammation may contribute to alleviating the NPS cluster in cancer patients.
头颈癌（HNC）患者可能会出现多种同时存在的神经心理症状（NPS）集群，包括疲劳、抑郁、疼痛、睡眠障碍和认知障碍。虽然炎症被认为是其中一些症状的关键机制，但其与作为一组症状的NPS之间的关联尚不清楚。因此，本研究的目的是探讨头颈癌患者在癌症治疗（放疗加或不加化疗）过程中外周炎症与NPS集群之间的关联。
招募头颈癌患者，并在治疗前、治疗结束时、治疗后三个月和一年进行随访。在这4个时间点收集血浆炎症标志物，包括C反应蛋白（CRP）、肿瘤坏死因子-α（TNFA）、可溶性肿瘤坏死因子受体-2（sTNFR2）、白细胞介素-1β（IL1-β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、单核细胞趋化蛋白-1（MCP-1）和白细胞介素-1受体拮抗剂（IL-1RA）以及患者报告的NPS集群。使用线性混合效应模型和控制协变量的广义估计方程（GEE）模型分析炎症标志物与NPS集群之间的关联。
147名头颈癌患者符合分析条件。56%的患者接受了放化疗作为治疗。治疗结束时报告的NPS集群得分最高，随后随时间逐渐下降。包括CRP、sTNFR2、IL-6和IL-1RA在内的炎症标志物升高与更高的连续性NPS集群得分相关（分别为p<0.001、p = 0.003、p<0.001、p<0.001）。GEE进一步证实，至少有两种中度症状的患者sTNFR2、IL-6和IL-1RA升高（分别为p = 0.017、p = 0.038、p = 0.008）。值得注意的是，NPS集群与炎症标志物之间的这种正相关在治疗后一年时对于CRP（p = 0.001）、sTNFR2（p = 0.006）和IL-1RA（p = 0.043）仍然显著。
大多数头颈癌患者随时间推移会出现NPS集群，尤其是在治疗结束后即刻。以炎症标志物为代表的炎症升高与随时间推移更严重的NPS集群密切相关；这种趋势在治疗后一年时也很明显。我们的研究结果表明，外周炎症在包括长期随访在内的癌症治疗过程中的NPS集群中起关键作用。减少外周炎症的干预措施可能有助于减轻癌症患者的NPS集群。
